Malaria is a major global health that affects half of the world population and kills approximately 2 million people each year. The global economic toll of malaria is enormous. Most of the current drugs against the disease are ineffective because of widespread prevalence of drug resistant strains. Therefore, it is urgent to identify new drug leads for the development of next generation of therapeutics against malaria. Marine biodiversity is particularly rich in novel chemical entities and has not been explored extensively for antimalarial drug discovery. This project will utilize unique capability of Harbor Branch Oceanographic Institute to procure samples from diverse marine ecosystems, often at a depth of 3000 ft using manned submersibles. The long-term goal is to develop novel malaria therapeutics from marine natural products. The objective of this application is to identify antimalarial compounds from marine macroorganisms. The rationale for this project is that marine macroorganisms have a very high likelihood to yield novel chemotypes because of their high diversity and have not been extensively explored for antimalarial development. Thus, the proposed research is relevant to NIH's mission that pertains to reduce the burden of human disease. Guided by supporting preliminary data two specific aims will be pursued: (1) Screen 3,000 peak marine natural product fractions, collected from unique marine ecosystems, for their ability to inhibit intraerythrocytic growth of Plasmodium falciparum. (2) Deconvolute active fractions and define the structure of bioactive components using chromatographic and spectroscopic procedures. The proposed research is significant because at the end of this project we expect to have a portfolio of antimalarial "hits". PUBLIC HEALTH RELEVANCE: This project will identify novel chemical entities that can be developed into drug leads for malaria therapy.